Fungicides are compounds, of natural or synthetic origin, which act to protect and cure plants against damage caused by agriculturally relevant fungi. Generally, no single fungicide is useful in all situations. Consequently, research is ongoing to produce fungicides that may have better performance, are easier to use, and cost less.
The present disclosure relates to 5-fluoro pyrimidine compounds and their use as fungicides. The compounds of the present disclosure may offer protection against ascomycetes, basidiomycetes, deuteromycetes and oomycetes.
One embodiment of the present disclosure may include compounds of Formula I:
wherein R1 is —N(R3)R4;R2 is —OR21;R3 is:                H;        C1-C6 alkyl optionally substituted with 1- to 3 R5;        C2-C6 alkenyl optionally substituted with 1-3 R5;        a 5- or 6-membered heteroaromatic ring selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl, each heteroaromatic ring being optionally substituted with 1-3 R30;        imidazole fused with an aromatic or heteroaromatic ring selected from the group consisting of benzene, oxazole, isoxazole, furan, thiazole, pyrimidine, pyridine, pyrrole, pyrazine, thiophene, each aromatic or heteroaromatic ring being optionally substituted with 1 to 3 R30;        benzo[1,3]dioxolyl;        3H-isobenzofuran-1-onyl;        cyano;        C3-C6 alkynyl optionally substituted with 1-3 R5;        —C(═O)R6;        —C(═O)OCH2C(═O)R8;        —C(═S)R6;        —C(═S)NHR8;        —C(═O)N(R8)R10;        —OR7;        —P(O)(OR15)2;        —S(O)2R8;        —SR8;        —Si(R8)3;        —N(R9)R10;        —N═C(R15)R16;        —(CHR22)mR37;        —(CHR24)OR29;        —C(═NR16)SR16; or        —C(═NR27)NR13R28;wherein m is an integer from 1-3;R4 is:        H;        hydroxyl;        amino;        C1-C6 alkyl, optionally substituted with 1-3 R5;        —C(═O)R6; or        —C(═O)N(R8)R10);alternatively R3 and R4 may be taken together to form:        a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;        ═C(R12)N(R13)R14;        ═C(R13)(R14);        ═C(R15)OR15;        ═S(R34)2; or        ═NR35;R5 is independently halogen, C1-C6 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 haloalkylthio, amino, C1-C3 alkylamino, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyl, C2-C6 alkylaminocarbonyl, —OH, N-methyl piperazine or C3-C6 trialkylsilyl;R6 is independently H, C1-C6 alkyl, C2-C6 alkenyl optionally substituted with 1-3 R30, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy C2-C6 alkoxycarbonyl, C1-C4 alkoxyalkoxy, C2-C6 alkylaminocarbonyl; 1-benzo[1,2,3]thiadiazol-7-yl, thiazolyl, benzyl, phenyl, phenoxy, or benzyloxy wherein the thiazolyl, benzyl, phenyl, phenoxy, or benzyloxy may be optionally substituted with 1-3 R20, a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;R7 is H, C1-C6 alkyl, C2-C6 alkenyl, C1-C5 haloalkyl, benzyl which may be optionally substituted with 1-5 R20, —CHR18C(O)OR19, —(CHR27)R28, —Si(R8)3, or a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;R8 is independently C1-C6 alkyl, C1-C6 haloalkyl, amino, C1-C6 alkylamino, C2-C6 dialkylamino, methylene-2-furanyl, —CHR15C(O)OR19, benzyl optionally substituted with 1-3 R30, phenyl optionally substituted with 1-3 R30, or a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;R9 is H, C1-C6 alkyl C1-C6 haloalkyl, —C(═O)R17, benzothiazoyl, quinazolinyl, or phenyl optionally substituted with 1-3 R20, a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;R10 is H or C1-C6 alkyl, C1-C6 haloalkyl, or phenyl optionally substituted with 1-3 R20;R11 is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, amino, C1-C6 alkylamino, C2-C6 dialkylamino, C2-C6 alkoxycarbonyl, or C2-C6 alkylcarbonyl;R12 is H or C1-C4 alkyl;R13 and R14 are independently H, cyano, —OH, C1-C4 alkyl, C1-C6 alkoxy, C2-C6, alkylcarbonyl, phenyl, or benzyl wherein the phenyl or benzyl may be optionally substituted with 1-3 R20;alternatively R13 and R14 may be taken together to form:        a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11, or 3,4-dihydro-1H-isoquinolin-2-yl;alternatively R12 and R13 may be taken together to form:        a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;R15 is H or C1-C6 alkyl, C2-C6 alkenyl, 2-benzofuranyl, a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;R16 is H, C1-C6 alkyl, or phenyl optionally substituted with 1-3 R20;alternatively R15 and R16 may be taken together as —(CH2)4— or —(CH2)5—;R17 is H, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 haloalkyl, C1-C6 alkoxy, benzyl, phenyl, phenoxy, or benzyloxy wherein each ring may be optionally substituted with 1-3 R20, a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;R18 is H, C1-C6 alkyl, or C1-C6 haloalkyl;R19 is H, C1-C6 alkyl, C1-C6 haloalkyl, or benzyl;R20 is independently halogen, cyano, nitro, amino, C1-C6 alkoxyalkoxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, hydroxyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C3-C6 alkynyloxy, C3-C6 haloalkynyloxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C2-C6 alkenylthio, C2-C6 haloalkenylthio, C2-C6 haloalkenylsulfonyl, C3-C6 alkynylthio, C3-C6 alkynylsulfonyl, C3-C6 haloalkynylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3-C8 dialkylaminocarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyl, C3-C6 trialkylsilyl, 2-[(E)-methoxyimino]-N-methyl-acetamidyl, phenyl, benzyl, benzyloxy, phenoxy, or a 5- or 6-membered heteroaromatic ring wherein each phenyl, benzyl, benzyloxy, phenoxy, or 5- or 6-membered heteroaromatic ring may be optionally substituted with 1-3 substitutents independently selected from R31;R21 is:        H;        C1-C14 alkyl;        C1-C6 haloalkyl;        C2-C4 alkenyl;        C2-C4 haloalkenyl;        C3-C4 alkynyl;        C3-C4 haloalkynyl;        phenyl, naphthyl, or tetrahydroquinolinyl each optionally substituted with 1-3 R20;        —(CHR22)mR23;        —(CHR24)mC(O)OR25;        —(CHR24)mC(O)R26;        —(CHR24)mC(O)N(R27)R28;        —(CHR24)mOR29;        —(CHR24)mSR29         —(CHR24)mN(R27)R28;        —C(═O)R32;        —N═C(R32)(R36);        —NR25C(═O)OR25         —Si(R8)3;        —SO2R33;        C2-C6 alkoxy carbonyl;        C2-C6 alkylaminocarbonyl;        C2-C6 alkylcarbonyl;        sugars selected from the group consisting of beta-D-glucose-tetraacetate, rhamnose, fructose, and pentose; or        a 5- or 6-membered heteroaromatic ring selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, triazolyl or isoxazolyl wherein each 5- or 6-member heteroaromatic ring may be optionally substituted with 1-5 R20;R22 is independently:        H;        halogen;        cyano;        nitro;        C1-C6 alkyl;        C1-C6 haloalkyl;        phenyl or benzyl optionally substituted with 1-3 R20;        C1-C6 hydroxyalkyl;        C2-C6 alkoxylalkyl;        C3-C6 haloalkynyl;        C2-C6 alkenyl;        C2-C6 haloalkenyl;        C3-C6 alkynyl;        C1-C6 alkoxy;        C1-C6 haloalkoxy;        C1-C6 alkylthio;        C1-C6 alkylamino;        C2-C8 dialkylamino;        C3-C6 cycloalkylamino;        C4-C6 (alkyl)cycloalkylamino;        C2-C6 alkylcarbonyl;        C2-C6 alkoxycarbonyl;        C2-C6 alkylaminocarbonyl;        C3-C8 dialkylaminocarbonyl;        C3-C6 trialkylsilyl;        ring-fused heteroaromatic rings selected from the group consisting of benzothiophenyl, quinolinyl, isoquinolinyl, thieno[2,3-b]pyridyl, 1-methyl-1H-thieno[2,3-c]pyrazolyl, and benzoimidazolyl, wherein each of the rings may be further substituted with 1-3 R20; or        a 5- or 6-membered heteroaromatic ring selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl and thienyl;R23 is:        H;        halogen;        C1-C6 alkyl;        C1-C6 haloalkyl;        C2-C6 dialkylamino;        phenyl optionally substituted with 1-5 R20;        ring-fused heteroaromatic rings selected from the group consisting of benzothiophenyl, quinolinyl, isoquinolinyl, thieno[2,3-b]pyridyl, 1-methyl-1H-thieno[2,3-c]pyrazolyl, benzofuranyl and benzoimidazolyl, 2,3-dihydrobenzofuran-2-yl, 4-methyl-4H-thieno[3,2-b]pyrrol-5-yl, 1-methyl-1H-indol-5-yl, imidazo[1,2-a]pyridin-2-yl, imidazo[2,1-b]thiazol-6-yl, benzothiazol-2-yl, benzo[b]thiophen-7-yl, and 1-methyl-1H-indazol-3-yl, wherein each of the rings may be further substituted with 1-3 R20;        naphthyl;        benzo[1,3]dioxolyl;        pyrrolidinonyl;        oxetanyl;        C1-C6 alkylthio optionally substituted with 1-5 R20;        a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11; or        a 5- or 6-membered heteroaromatic ring selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl, imidazolyl, thiophene-2-yl and thiophen-3-yl wherein each heteroaromatic ring may be optionally substituted with 1-3 R20;R24 is H, C1-C6 alkyl, C1-C6 alkoxy, benzyl, or phenyl wherein each of the benzyl or phenyl may be optionally substituted with 1-3 R20;R25 is H, C1-C6 alkyl, phenyl or benzyl optionally substituted with 1-3 R20;R26 is:        H;        C1-C6 alkyl;        C1-C6 alkoxy;        phenyl optionally substituted with 1-3 R20; or        a 5- or 6 membered heteroaromatic ring selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, triazolyl and isoxazolyl;R27 and R28 are independently:        H;        C1-C6 alkyl;        benzyl or phenyl wherein each of the benzyl or phenyl may be optionally substituted with 1-3 R20; or        a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;R29 is:        H;        C1-C6 alkyl;        C1-C6 haloalkyl;        C1-C6 alkoxyalkyl;        C2-C6 alkylcarbonyl;        benzyl, benzoyl, or phenyl wherein each of the benzyl, benzoyl or phenyl may be optionally substituted with 1-3 R20; or        a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;R30 is independently halogen, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, hydroxyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C3-C6 alkynyloxy, C3-C6 haloalkynyloxy, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C2-C6 alkenylthio, C2-C6 haloalkenylthio, C2-C6 haloalkenylsulfonyl, C3-C6 alkynylthio, C3-C6 alkynylsulfonyl, C3-C6 haloalkynylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3-C8 dialkylaminocarbonyl, C3-C6 trialkylsilyl, thiazolyl, phenyl, pyrimidinyl, or pyridyl, wherein the thiazolyl, phenyl, pyridyl, or pyrimidinyl may be optionally substituted with 1-3 R20;R31 is independently halogen, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, hydroxyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C3-C6 alkynyloxy, C3-C6 haloalkynyloxy, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C2-C6 alkenylthio, C2-C6 haloalkenylthio, C2-C6 haloalkenylsulfonyl, C3-C6 alkynylthio, C3-C6 alkynylsulfonyl, C3-C6 haloalkynylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3-C8 dialkylaminocarbonyl, or C3-C6 trialkylsilyl;R32 is independently:        C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, hydroxyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C3-C6 alkynyloxy, C3-C6 haloalkynyloxy, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C2-C6 alkenylthio, C2-C6 haloalkenylthio, C2-C6 haloalkenylsulfonyl, C3-C6 alkynylthio, C3-C6 alkynylsulfonyl, C3-C6 haloalkynylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3-C8 dialkylaminocarbonyl, C3-C6 trialkylsilyl;        phenyl wherein the phenyl ring may be optionally substituted with 1-3 R20; or        a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;R33 is independently:        C1-C6 alkyl, C1-C6 haloalkyl, phenyl or thienyl optionally substituted with 1-3 R20; or        a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;R34 is:        C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkoxyalkyl, C1-C6 alkylamino; or        a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;R35 is:        C1-C6 alkyl, C2-C6 alkylcarbonyl; or        a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;R36 is H, cyano, C1-C6 alkyl, C1-C6 alkoxy, benzyl, or phenyl wherein each of the benzyl, or phenyl may be optionally substituted with 1-3 R20;alternatively R32 and R36 may be taken together to form:        a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11; andR37 is independently:        H, halogen, or phenyl optionally substituted with 1-5 R20;        C1-C6 alkyl, C1-C6 haloalkyl, hydroxyl, C1-C6 alkoxy, or C1-C6 haloalkoxy; or        a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11.        
Another embodiment of the present disclosure may include a fungicidal composition for the control or prevention of fungal attack comprising the compounds described above and a phytologically acceptable carrier material.
Yet another embodiment of the present disclosure may include a method for the control or prevention of fungal attack on a plant, the method including the steps of applying a fungicidally effective amount of one or more of the compounds described above to at least one of the fungus, the plant, an area adjacent to the plant, and the seed adapted to produce the plant.
The term “alkyl” refers to an unbranched, branched, or cyclic carbon chain, including methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tertiary butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.
The term “alkenyl” refers to a branched, unbranched or cyclic carbon chain containing one or more double bonds including ethenyl, propenyl, butenyl, isopropenyl, isobutenyl, cyclohexenyl, and the like.
The term “alkynyl” refers to refers to a branched or unbranched carbon chain containing one or more triple bonds including propynyl, butynyl and the like.
As used throughout this specification, the term ‘R’ refers to the group consisting of C2-8 alkyl, C3-8 alkenyl or C3-8 alkynyl, unless stated otherwise.
The term “alkoxy” refers to an —OR substituent.
The term “alkoxycarbonyl” refers to a —C(O)—OR substituent.
The term “alkylcarbonyl” refers to a —C(O)—R substituent.
The term “alkylsulfonyl” refers to an —SO2—R substituent.
The term “haloalkylsulfonyl” refers to a sulfonyl substitution on an alkyl which is partially substituted with halogen atoms.
The term “alkylthio” refers to an —S—R substituent.
The term “alkylaminocarbonyl” refers to a —C(O)—N(H)—R substituent.
The term “dialkylaminocarbonyl” refers to a —C(O)—NR2 substituent.
The term “alkylcycloalkylamino” refers to a cycloalkylamino substituent that is substituted with an alkyl group.
The term “trialkylsilyl” refers to —SiR3.
The term “cyano” refers to a —C≡N substituent.
The term “hydroxyl” refers to a —OH substituent
The term “amino” refers to a —NH2 substituent
The term “alkylamino” refers to a —N(H)—R substituent
The term “dialkylamino” refers to a —NR2 substituent
The term “alkoxyalkoxy” refers to —O(CH2)nO(CH2)n where n is an integer from 1-3
The term “alkoxyalkyl” refers to an alkoxy substitution on an alkyl.
The term “haloalkoxyalkyl” refers to an alkoxy substitution on an alkyl which may be partially substituted with halogen atoms
The term “hydroxyalkyl” refers to an alkyl which is substituted with a hydroxyl group.
The term “haloalkoxy” refers to a —OR—X substituent, wherein X is Cl, F, Br, or I, or any combination thereof.
The term “haloalkyl” refers to an alkyl, which is substituted with Cl, F, I, or Br or any combination thereof.
The term “haloalkenyl” refers to an alkenyl, which is substituted with Cl, F, I, or Br or any combination thereof.
The term “haloalkynyl” refers to an alkynyl which is substituted with Cl, F, I, or Br or any combination thereof.
The term “halogen” or “halo” refers to one or more halogen atoms, defined as F, Cl, Br, and I.
The term “hydroxycarbonyl” refers to a —C(O)—OH substituent.
The term “nitro” refers to a —NO2 substituent.
The term “thienyl” refers to a 5-member aromatic ring with one sulfur atom.
Throughout the disclosure, reference to the compounds of Formula I is read as also including optical isomers and salts of Formula I, and hydrates thereof. Specifically, when Formula I contains a branched chain alkyl group, it is understood that such compounds include optical isomers and racemates thereof. Exemplary salts include: hydrochloride, hydrobromide, hydroiodide, and the like.
It is also understood by those skilled in the art that additional substitution is allowable, unless otherwise noted, as long as the rules of chemical bonding and strain energy are satisfied and the product still exhibits fungicidal activity.
Another embodiment of the present disclosure is a use of a compound of Formula I, for protection of a plant against attack by a phytopathogenic organism or the treatment of a plant infested by a phytopathogenic organism, comprising the application of a compound of Formula I, or a composition comprising the compound to soil, a plant, a part of a plant, foliage, and/or seeds.
Additionally, another embodiment of the present disclosure is a composition useful for protecting a plant against attack by a phytopathogenic organism and/or treatment of a plant infested by a phytopathogenic organism comprising a compound of Formula I and a phytologically acceptable carrier material.